Macrolactin XY, a Macrolactin Antibiotic from Marine-Derived Bacillus subtilis sp. 18.

Two new compounds, macrolactin XY (1) and (5R, 9S, 10S)-5-(hydroxymethyl)-1,3,7-decatriene-9,10-diol (2), together with nine known compounds (3-11) were isolated from the marine Bacillus subtilis sp. 18 by the OSMAC strategy. These compounds were evaluated for antibacterial activity against six tested microorganisms. Compounds 1-5 and 7-10 showed varied antibacterial activity, with the minimum inhibitory concentration (MIC) ranging from 3 to 12 μg/mL. Macrolactin XY (1) was found to possess superior antibacterial activity, especially exhibiting significant effectiveness against Enterococcus faecalis. The antibacterial activity mechanism against E. faecalis was investigated. The mechanism may disrupt bacterial cell membrane integrity and permeability, and also inhibit the expression of genes associated with bacterial energy metabolism, as established by the experiments concerning cell membrane potential, SDS-PAGE electrophoresis, cell membrane integrity, and key gene expressions. This study offers valuable insights and serves as a theoretical foundation for the future development of macrolactins as antibacterial precursors.